Gadolinium complexes of macrocyclic diethylenetriamine-N-oxide pentaacetic acid-bisamide as highly stable MRI contrast agents with high relaxivity. Issue 26 (19th June 2020)

• Record Type: Journal Article
• Authors: Xu, Kehan; Xu, Na; Zhang, Beibei; Tang, Weijun; Ding, Yun; Hu, Aiguo
• Is Part Of: Dalton transactions. Volume 49:Issue 26(2020)
• Page Start: 8927
• Page End: 8932
• Publication Date: 2020-06-19
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d0dt00248h
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Macrocyclic gadolinium(iii ) complexes with hyphenated-amino- N -oxide (HAO) type ligand structures are designed as efficient magnetic resonance imaging (MRI) contrast agents (CAs) with high relaxivity and stability. Abstract : Gadolinium(iii ) complexes are generally considered efficient magnetic resonance imaging (MRI) contrast agents (CAs) and widely used in clinical applications. High relaxivity and stability are two essential criteria for a Gd(iii )-complex to be used as a MRI-CA. One crucial strategy to achieve high relaxivity for small molecular Gd(iii )-based MRI contrast agents is to increase the hydration number q . Meanwhile, metal complexes with macrocyclic ligands have been proved to inherit high thermodynamic stability and kinetic inertness. Herein, a series of macrocyclic ligands based on diethylenetriamine- N -oxide pentaacetic acid-bisamide were synthesized. Among them, cyclo-DTPA-NO-C6O2 (3d ) was the strongest ligand for Gd(iii ) as confirmed by experimental results. The hydration number of the Gd-cyclo-DTPA-NO-C6O2 (4d ) complex was characterized by luminescence measurements to be 3 and the coordination structure was confirmed with computational simulations. Consequently, the relaxivity of this complex (14.3 mM −1 s −1, 1.5 T, 25 °C) is about triple that of commercial MRI CAs. The conditional stability constant of the Gd(iii ) complex, pGd, calculated from spectrophotometric titration studies, was comparable to that of one of the most stable commercial MRI-CAs, Gd-DTPA (Magnevist®). Meanwhile, the kinetic inertness of the complex was even higher than that of Gd-DTPA thanks to its macrocyclic coordination structure.